BIOCHEM CHAPTER 16
(G6P generates glucose in the liver) G6P is produced in ________ G6Pase is in the ER membrane thus, G6P must be transported to ER by G6P translocase before it can be ________ resulting ________ and ____ are returned to cytosol glucose leaves liver by GLUT2 glucose transporter **muscle and other tissues lack G6Pase and thus retain their G6P
(G6P generates glucose in the liver) G6P is produced in cytosol G6Pase is in the ER membrane thus, G6P must be transported to ER by G6P translocase before it can be hydrolyzed resulting glucose and Pi are returned to cytosol glucose leaves liver by GLUT2 glucose transporter **muscle and other tissues lack G6Pase and thus retain their G6P
(Gluconeogenesis requires metabolite transport between mitochondria & cytosol) (1) oxaloacetate--(aspartate aminotransferase)--> aspartate (does ________ involve NADH)
(Gluconeogenesis requires metabolite transport between mitochondria & cytosol) (1) oxaloacetate--aspartate aminotransferase--> aspartate (does not involve NADH)
(Gluconeogenesis requires metabolite transport between mitochondria & cytosol) -________ occurs in mitochondria -enzymes that convert PEP->glucose are ________ -PEP ________ be directly transported across mitochondrial membrane -oxaloacetate ________ be directly transported across mitochondrial membrane (1) oxaloacetate--(aspartate aminotransferase)--> aspartate (2) oxaloacetate --(malate dehydrogenase + NADH + H+)-->malate (2) also transfers NADH reducing equivalents to the cytosol
(Gluconeogenesis requires metabolite transport between mitochondria & cytosol) -oxaloacetate occurs in mitochondria -enzymes that convert PEP->glucose are cytosolic -PEP CAN be directly transported across mitochondrial membrane -oxaloacetate CANNOT be directly transported across mitochondrial membrane (1) oxaloacetate--aspartate aminotransferase--> aspartate (2) oxaloacetate --malate dehydrogenase + NADH + H+-->malate (2) also transfers NADH reducing equivalents to the cytosol
(Gluconeogenesis requires metabolite transport between mitochondria & cytosol) in species with cytosolic PEPCK, oxaloacetate must first be converted either to ________ or to ________
(Gluconeogenesis requires metabolite transport between mitochondria & cytosol) in species with cytosolic PEPCK, oxaloacetate must first be converted either to aspartate or to malate
(Gluconeogenesis requires metabolite transport between mitochondria & cytosol) oxaloacitate transport route (2) uses ________ NADH and produces ________ NADH , which is needed for gluconeogenisis in the cytosol (produces NADH at the final oxaloacetate destination) [ oxaloacetate --(malate dehydrogenase + NADH + H+)-->malate ] *slide 15
(Gluconeogenesis requires metabolite transport between mitochondria & cytosol) oxaloacitate transport route (2) uses mitochondrial NADH and produces cytosolic NADH , which is needed for gluconeogenisis in the cytosol [ oxaloacetate --malate dehydrogenase + NADH + H+-->malate ]
(Gluconeogenesis) -occurs in ________ (and a teensy in kidney) **slide 14
(Gluconeogenesis) -occurs in liver (and a teens in kidney) **slide 14
(Gluconeogenesis) know structure of biotin
(Gluconeogenesis) know structure of biotin
(Gluconeogenesis) non carbohydrate precursers able to be converted to ____________ & then to glucose: -_______ -pyruvate -citric acid cycle intermediates (including oxaloacetate) -AA (except leucine and lysine) **no acetyl coA or fatty acids (though F.A. breakdown=>ATP that powers _______________)
(Gluconeogenesis) non carbohydrate precursers able to be converted to oxaloacetate & then to glucose: -lactate -pyruvate -citric acid cycle intermediates (including oxaloacetate) -AA (except leucine and lysine) **no acetyl coA or fatty acids (though F.A. breakdown=>ATP that powers gluconeogenesis)
(Gluconeogenesis) step#1 pyruvate is converted to ______________ (PEP) in 2 steps pyruvate --(pyruvate carboxylase)--> ___________ --(PEP carboxykinase (PEPCK))--> PEP -pyruvate carboxylase = homotetramer w/________ cofactor attached to each monomer -phase 1 of pyr. carb.: three step reaction; carboxyphosphate is formed from bicarbonate and ATP---generation of CO2---carboxylates biotin -phase 2 of pyr. carb.: three step rxn; CO2 produced at active site cia elimination of biotinyl-enzyme---which accepts a proton from pyruvate to generate pyruvate enolate----enolate nucleophilically attaches the CO2=>oxaloacetate -oxaloacetate is a high energy intermediate (the 'activated' form of pyruvate) -PEPCK removes the CO2 to form PEP
(Gluconeogenesis) step#1 pyruvate is converted to phosphoenolpyruvate (PEP) in 2 steps pyruvate --pyruvate carboxylase--> oxaloacetate --PEP carboxykinase (PEPCK)--> PEP -pyruvate carboxylase = homotetramer w/biotin cofactor attached to each monomer -phase 1 of pyr. carb.: three step reaction; carboxyphosphate is formed from bicarbonate and ATP---generation of CO2---carboxylates biotin -phase 2 of pyr. carb.: three step rxn; CO2 produced at active site cia elimination of biotinyl-enzyme---which accepts a proton from pyruvate to generate pyruvate enolate----enolate nucleophilically attaches the CO2=>oxaloacetate -oxaloacetate is a high energy intermediate (the 'activated' form of pyruvate) -PEPCK removes the CO2 to form PEP
(Glycogen synthesis) -glycogen synth and breakdown occur by separate pathways -synthesis of glycogen from G1P under physiological conditions is thermodynamically ________ -glycogen breakdown is ________ ________ process of glycogen breakdown is reversed by a process that uses UTP to generate a UDP-glucose intermediate
(Glycogen synthesis) -glycogen synth and breakdown occur by separate pathways -synthesis of glycogen from G1P under physiological conditions is thermodynamically unfavorable -glycogen breakdown is exergonic exergonic process of glycogen breakdown is reversed by a process that uses UTP to generate a UDP-glucose intermediate
(control of glycogen metabolism) _______, being a trigger for both phosphorylase kinase (--> glycogen phosphorylase=>glycogen breakdown) and muscle contraction. rate of glycogen breakdown & rate of ________ contraction = linked glycogen breakdown provides fuel for glycolysis to generate ______ muscles need
(control of glycogen metabolism) Ca2+, being a trigger for both phosphorylase kinase (--> glycogen phosphorylase=>glycogen breakdown) and muscle contraction. rate of glycogen breakdown & rate of muscle contraction = linked glycogen breakdown provides fuel for glycolysis to generate ATP muscles need
(control of glycogen metabolism) Phosphorylase kinase (PhK) is a serine/threonine-specific protein kinase which activates ________ ___________ to release glucose-1-phosphate from glycogen. The protein is a homotetramer of tetramers arranged in an approximate "butterfly" shape. Each of the four tetramers is composed of an α, β, γ and δ subunit. The γ subunit is the site of the enzyme's catalytic activity while the other three subunits serve ________ functions. When unmodified, the α and β subunits ________ the enzyme's catalysis, but phosphorylation of both these subunits by ________________ (PKA, or cAMP-dependent protein kinase) reduces their respective inhibitory activities.
(control of glycogen metabolism) Phosphorylase kinase (PhK) is a serine/threonine-specific protein kinase which activates glycogen phosphorylase to release glucose-1-phosphate from glycogen. The protein is a homotetramer of tetramers arranged in an approximate "butterfly" shape. Each of the four tetramers is composed of an α, β, γ and δ subunit. The γ subunit is the site of the enzyme's catalytic activity while the other three subunits serve regulatory functions. When unmodified, the α and β subunits inhibit the enzyme's catalysis, but phosphorylation of both these subunits by protein kinase A (PKA, or cAMP-dependent protein kinase) reduces their respective inhibitory activities.
(control of glycogen metabolism) glycogen phosphorylase is activated by phosphorylation: cascade: (+, phosphorylates) PKA (+, phosphorylates) phosphorylase kinase (-, dephosphorylates) ___________ ________ (acts on both) **slide 9
(control of glycogen metabolism) glycogen phosphorylase is activated by phosphorylation: cascade: (+, phosphorylates) PKA (+, phosphorylates) phosphorylase kinase (-, dephosphorylates) phosphoprotein phosphatase (acts on both) **slide 9
(control of glycogen metabolism) glycogen phosphorylase-a ________ rate of glycogen breakdown catalyzes the ____________ step in glycogenolysis Glycogen phosphorylase breaks up glycogen into ________ subunits. Glycogen is left with _____ fewer glucose molecule, and the free glucose molecule is in the form of glucose-1-phosphate. In order to be used for metabolism, it must be converted to glucose-6-phosphate by the enzyme ________.
(control of glycogen metabolism) glycogen phosphorylase-a increases rate of glycogen breakdown catalyzes the rate-limiting step in glycogenolysis Glycogen phosphorylase breaks up glycogen into glucose subunits. Glycogen is left with one fewer glucose molecule, and the free glucose molecule is in the form of glucose-1-phosphate. In order to be used for metabolism, it must be converted to glucose-6-phosphate by the enzyme phosphoglucomutase.
(control of glycogen metabolism) phosphoprotein phosphatase-1 (PP1) ________ phosphoryl groups from: -glycogen phosphorylase-a -phosphorylase kinase _____ subunits
(control of glycogen metabolism) phosphoprotein phosphatase-1 (PP1) removes phosphoryl groups from: -glycogen phosphorylase-a -phosphorylase kinase a&B subunits
(control of glycogen metabolism) phosphorylase kinase: -is activated by ______________ & Ca2+ -PKA phosphorylates its a and B subunits -heterotetramer: alpha,beta,gamma,delta - gamma is ________ site -aB are phosphorylated to be active -y is ________ by a short segment of its sequence (conformationally moved upon phosphorylation of aB subunits by PKA) -delta is ________, binding of Ca2+
(control of glycogen metabolism) phosphorylase kinase: -is activated by phosphorylation & Ca2+ -PKA phosphorylates its a and B subunits -heterotetramer: alpha,beta,gamma,delta - gamma is catalytic site -aB are phosphorylated to be active -y is autoinhibited by a short segment of its sequence (conformationally moved upon phosphorylation of aB subunits by PKA) -delta is calmodulin, binding of Ca2+
(control of glycogen metabolism) phosphorylase kinase: ___ & ___ subunits: subject to phosphorylation y subunit: NOT subject to phosphorylation
(control of glycogen metabolism) phosphorylase kinase: a & B subunits: subject to phosphorylation y subunit: NOT subject to phosphorylation
(control of glycogen metabolism: Glycogen phosphorylase and glycogen synthase are under allosteric control) setting of high [ATP] high [G6P]: *state increase or decrease* =>(__) glycogen phosphorylase =>(__) glycogen synthase ===> (__) glycogen synthesis
(control of glycogen metabolism: Glycogen phosphorylase and glycogen synthase are under allosteric control) setting of high [ATP] high [G6P]: =>(-) glycogen phosphorylase =>(+) glycogen synthase ===> (+) glycogen synthesis
(control of glycogen metabolism: Glycogen phosphorylase and glycogen synthase are under allosteric control) setting of low [ATP] low [G6P]: =>(+) glycogen phosphorylase =>(-) glycogen synthase ===> (+) glycogen breakdown
(control of glycogen metabolism: Glycogen phosphorylase and glycogen synthase are under allosteric control) setting of low [ATP] low [G6P]: =>(+) glycogen phosphorylase =>(-) glycogen synthase ===> (+) glycogen breakdown
(control of glycogen metabolism: Glycogen phosphorylase and glycogen synthase are under covalent modification control) enzymatically interconvertible enzyme systems: -glycogen phosphorylase is active ________-P (________ --(phosphorylates)--> ___________ ________ --(phosphorylates)-->glycogen phosphorylase) -glycogen synthase is active WITHOUT (P)
(control of glycogen metabolism: Glycogen phosphorylase and glycogen synthase are under covalent modification control) enzymatically interconvertible enzyme systems: -glycogen phosphorylase is active WITH-P (PKA --(phosphorylates)--> phosphorylase kinase --(phosphorylates)-->glycogen phosphorylase) -glycogen synthase is active WITHOUT (P)
(gluconeogenesis and glycolysis are independently regulated) -low [________] =>glucagon secretion=>increased [________] =>activates PKA =>enzyme phosphorylation =>inactivates PFK-2 =>activates FBP-ase =>decreased [F2,6P] =>increased gluconeogenesis see slide 16
(gluconeogenesis and glycolysis are independently regulated) -low [glucose] =>glucagon secretion=>increased [cAMP] =>activates PKA =>enzyme phosphorylation =>inactivates PFK-2 =>activates FBP-ase =>decreased [F2,6P] =>increased gluconeogenesis see slide 16
(gluconeogenesis and glycolysis are independently regulated) Fructose-2,6-Bisphosphate (F2,6P) activates _____________ (glycolysis) and inhibits fructose-1,6-bisphosphatase (gluconeogenesis) so overall F2,6P => glycolysis
(gluconeogenesis and glycolysis are independently regulated) Fructose-2,6-Bisphosphate (F2,6P) activates phosphofructokinase (glycolysis) and inhibits fructose-1,6-bisphosphatase (gluconeogenesis)
(gluconeogenesis and glycolysis are independently regulated) gluconeogenesis and glycolysis are independantly regulated, so that all rxns are ________ **slide 15
(gluconeogenesis and glycolysis are independently regulated) gluconeogenesis and glycolysis are independantly regulated, so that all rxns are exergonic **slide 15
(glycogen metabolism is subject to hormonal control (insulin and glucagon)) insulin (lowers BS) and glucagon (raises BS) are both made in the ________ *referring to glucose*
(glycogen metabolism is subject to hormonal control (insulin and glucagon)) insulin (lowers BS) and glucagon (raises BS) are both made in the pancrease
(glycogen metabolism is subject to hormonal control) increased cAMP -> increased ________ activity -> increases phosphorylation rates (of phosphorlase kinase(on), of glycogen phosphorylase(on) and of glycogen synthase(off)=> glycogen ________ => glycolysis
(glycogen metabolism is subject to hormonal control) increased cAMP -> increased PKA activity -> increases phosphorylation rates (of phosphorlase kinase(on), of glycogen phosphorylase(on) and of glycogen synthase(off)=> glycogen breakdown => glycolysis
(glycogen metabolism is subject to hormonal control) hormones affect metabolism in their target cells by stimulating ________ modification (phosphorylation) of regulatory enzymes through the binding of transmembrane receptors and the release of 2nd messengers (cAMP)
(glycogen metabolism is subject to hormonal control) hormones affect metabolism in their target cells by stimulating covalent modification (phosphorylation) of regulatory enzymes through the binding of transmembrane receptors and the release of 2nd messengers (cAMP)
(hormonal control of glycogen metabolism) insulin sensitive glucose transporter ________ (letting glucose in) are present in muscle & fat cells (not liver or brain). results in glycogen synthesis.
(hormonal control of glycogen metabolism) insulin sensitive glucose transporter GLUT4 (letting glucose in) are present in muscle & fat cells (not liver or brain). results in glycogen synthesis.
(hormonal control of glycogen metabolism) -epinephrin (from adrenal gland) binding to B-adrenoreceptors on liver and muscle cells=> increased [______] =>glycogen degradation to G6P => glycolysis in muscle or glucose export in liver **same response to glucagon, no glucagon acceptors on muscle ***slide 13
(hormonal control of glycogen metabolism) -epinephrin (from adrenal gland) binding to B-adrenoreceptors on liver and muscle cells=> increased [cAMP] =>glycogen degradation to G6P => glycolysis in muscle or glucose export in liver **same response to glucagon, no glucagon acceptors on muscle ***slide 13
(hormonal control of glycogen metabolism) -epinephrine (from adrenal gland) binding to a-Adrenoreceptors on liver cell => increased [______] => glycogen degradation => glucose export
(hormonal control of glycogen metabolism) -epinephrine (from adrenal gland) binding to a-Adrenoreceptors on liver cell => increased [Ca2+] => glycogen degradation => glucose export
(hormonal control of glycogen metabolism) liver responds both to insulin and directly to increased glucose by increasing glycogen ________
(hormonal control of glycogen metabolism) liver responds both to insulin and directly to increased glucose by increasing glycogen synthesis
(hormonal control of glycogen metabolism) mechanism of insulin action: target enzyme PP1 (phosphorylation inhibition => glycogen ________) promoting the storage of glucose as ________
(hormonal control of glycogen metabolism) mechanism of insulin action: target enzyme PP1 (phosphorylation inhibition => glycogen synth) promoting the storage of glucose as glycogen
(other carbohydrate biosynthetic pathways) O-linked oligosaccharides: - are posttranslationally formed -synthesized in ________ ________ N-Linked oligosaccharides -more complicated -synthesis of an oligosaccharide with composition (N-acetylglucosamine)2(mannose)9(glucose)3 on a dolichol carrier ??? -sugar residues are added to the lipid carrier, dolichol pyrophosphate -dolichol anchors the growing oligosaccharide to the ER membrane (site of glycosylation) -??? slide 17
(other carbohydrate biosynthetic pathways) O-linked oligosaccharides: - are posttranslationally formed -synthesized in Golgi apparatus N-Linked oligosaccharides -more complicated -synthesis of an oligosaccharide with composition (N-acetylglucosamine)2(mannose)9(glucose)3 on a dolichol carrier -sugar residues are added to the lipid carrier, dolichol pyrophosphate -dolichol anchors the growing oligosaccharide to the ER membrane (site of glycosylation) -??? slide 17
(other carbohydrate biosynthetic pathways) nucleotide sugars power the formation of glycosidic bonds (synthesis of nucleotide sugar releases PPi, whose exergonic hydrolysis drives the rxn)
(other carbohydrate biosynthetic pathways) nucleotide sugars power the formation of glycosidic bonds (synthesis of nucleotide sugar releases PPi, whose exergonic hydrolysis drives the rxn)
**Glycogen is a polymer of glucose in (1-4) linkages with (1-6) linked branches every 8-14 residues **Glycogen is the storage ___________ in skeletal muscle and liver cells. **In glycogen breakdown, __________ residues are sequentially removed from the nonreducing ends. **The breakdown of glycogen in skeletal muscle ultimately supplies glucose-6-phosphate, which can enter ____________ to generate ______
**Glycogen is a polymer of glucose in (1-4) linkages with (1-6) linked branches every 8-14 residues **Glycogen is the storage polysaccharide in skeletal muscle and liver cells. **In glycogen breakdown, glucose residues are sequentially removed from the nonreducing ends. **The breakdown of glycogen in skeletal muscle ultimately supplies glucose-6phosphate, which can enter glycolysis to generate ATP
-muscles will not release glucose directly to blood -they release equivalents ________ (lactic acid) and ________ -muscle releases lactate & alanine to liver -> ________ -> releases glucose into ________ (liver is getting its energy to do this via fatty acid oxidation)
-muscles will not release glucose directly to blood -they release equivalents lactate (lactic acid) and alanine -muscle releases lactate & alanine to liver->gluconeogenesis->releases glucose into blood (liver is getting its energy to do this via fatty acid oxidation)
The body obtains glucose (either directly from the diet or from amino acids and lactate via _______________). Glucose either remains soluble in the body fluids or is stored in a polymeric form, glycogen. Glycogen is considered the principal storage form of glucose and is found mainly in liver and muscle, with kidney and intestines adding minor storage sites. Stores of glycogen in the ________ are considered the main buffer of blood glucose levels.
...
________ ________ (PC) is an enzyme of the ligase class that catalyzes the (depending on the species) irreversible carboxylation of pyruvate to form oxaloacetate (OAA) The enzyme is a mitochondrial protein containing a ________ prosthetic group,[1] requiring magnesium or manganese and acetyl CoA.
...
the following metabolic conversions occur in _______________: A) oxaloacetate -> phosphoenolpyruvate B) fructose-1,6-bisphosphate -> fructose-6-phosphate C) glucose-6-phosphate ->glucose D) NADH + -> H+ NAD+
...
A muscle cell takes a glucose molecule, stores it as part of a glycogen molecule and later releases it and sends it through glycolysis. What will be the net ATP yield?
2
3 enzymes of glycogen ________ (1) UDP-glucose pyrophosphorylase (2) glycogen synthase (3)glycogen branching enzyme
3 enzymes of glycogen synthesis (1) UDP-glucose pyrophosphorylase (2) glycogen synthase (3)glycogen branching enzyme
Biosynthesis requires the expenditure of free energy. Which metabolic conversion involved in glucose synthesis requires the direct expenditure of ATP free energy (ATP is also a reactant)?
3-Phosphoglycerate 1,3-bisphosphoglycerate
the net energetic cost of converting two pyruvate to one glucose by gluconeogenesis in ATP equivalents?
6
describe the role of fructose-2,6-bisphosphate (F2,6P) in liver cells
F2,6P is a potent allosteric activator of phosphofructokinase and an inhibitor of fructose bisphosphatase. (encouraging glucose breakdown)
Gluconeogenesis is a metabolic pathway that results in the generation of glucose from ______________ carbon substrates such as pyruvate, ________, glycerol, and glucogenic amino acids.
Gluconeogenesis is a metabolic pathway that results in the generation of glucose from non-carbohydrate carbon substrates such as pyruvate, lactate, glycerol, and glucogenic amino acids.
Glycogen forms an energy reserve that can be quickly mobilized to meet a sudden need for glucose. __________ represents the main storage form of glucose in the body. Found in the liver and muscles. Only the glycogen stored in the ________ can be made accessible to other organs.
Glycogen forms an energy reserve that can be quickly mobilized to meet a sudden need for glucose. Polysaccharide represents the main storage form of glucose in the body. Found in the liver and muscles. Only the glycogen stored in the liver can be made accessible to other organs.
Glycogen metabolism is controlled in part by __________ effectors such as AMP, ATP, & G6P. Covalent modificaiton of glycogen phosphorylase and glycogen synthase shifts their T<=>R equilibria and therefore alters their sensitivity to allosteric effectors
Glycogen metabolism is controlled in part by allosteric effectors such as AMP, ATP, & G6P. Covalent modificaiton of glycogen phosphorylase and glycogen synthase shifts their T<=>R equilibria and therefore alters their sensitivity to allosteric effectors
Glycogen phosphorylase can act only on ________ chains of glycogen (α1-4 glycosidic linkage). Its work will immediately come to a halt _____ residues away from α1-6 branch (which are exceedingly common in glycogen). In these situations, a ________ enzyme is necessary, which will straighten out the chain in that area. In addition, the enzyme transferase shifts a block of 3 glucosyl residues from the outer branch to the other end, and then a α1-6 glucosidase enzyme is required to break the remaining (single glucose) α1-6 residue that remains in the new linear chain. After all this is done, glycogen phosphorylase can continue.
Glycogen phosphorylase can act only on linear chains of glycogen (α1-4 glycosidic linkage). Its work will immediately come to a halt four residues away from α1-6 branch (which are exceedingly common in glycogen). In these situations, a debranching enzyme is necessary, which will straighten out the chain in that area. In addition, the enzyme transferase shifts a block of 3 glucosyl residues from the outer branch to the other end, and then a α1-6 glucosidase enzyme is required to break the remaining (single glucose) α1-6 residue that remains in the new linear chain. After all this is done, glycogen phosphorylase can continue.
In which cellular location does the synthesis of N-linked oligosaccharides take place?
Golgi apparatus
. If cAMP levels are high
It transfers an (14) linked trisaccharide unit from a limit branch to the nonreducing end of another branch, and then cleaves the (16) branch point releasing glucose.
describe the function of the glycogen debranching enzyme in glycogenolysis?
It transfers an (14) linked trisaccharide unit from a limit branch to the nonreducing end of another branch, and then cleaves the (16) branch point releasing glucose.
In liver cells, if cAMP concentrations are high
PFK-2/FBPase-2 will function to degrade F-2,6-P, thereby enhancing gluconeogenesis & depressing glycolysis.
Raffinose: -humans ________ have enzymes for its rapid degradation -________ degrades it faster, in the process =>CO2 -some bean types have high sulfur -flatulents due to CO2 from raffinose -smell due to sulfur
Raffinose: -humans do not have enzymes for its rapid degradation -bacteria degrades it faster, in the process =>CO2 -some bean types have high sulfur -flatulents due to CO2 from raffinose -smell due to sulfur
In glycogen synthesis, the intermediate between glucose-1-phosphate and glycogen is
UDP
UDPG (UDP-________ is an activated molecule)
UDPG (UDP-glucose is an activated molecule)
Water is prevented from entering the active site of the enzyme to prevent the ________ cleavage of glycogen. Glycogen phosphorylase phosphorolytically cleaves glycogen to produce ________. On the other hand, hydrolytic cleavage of glycogen would produce glucose, which would need to be ________ to enter glycolysis. Phosphorolytic cleavage is favored because the ATP needed to phosphorylate glucose is conserved. ________ supplies in muscle cells are maintained because the phosphorylated product, glucose-1-phosphate, cannot be transported out of the cell. Glucose-1-phosphate can then be converted to glucose-6-phosphate to enter glycolysis, meeting the energy needs of the muscle.
Water is prevented from entering the active site of the enzyme to prevent the hydrolytic cleavage of glycogen. Glycogen phosphorylase phosphorolytically cleaves glycogen to produce glucose 1-phosphate. On the other hand, hydrolytic cleavage of glycogen would produce glucose, which would need to be phosphorylated to enter glycolysis. Phosphorolytic cleavage is favored because the ATP needed to phosphorylate glucose is conserved. Energy supplies in muscle cells are maintained because the phosphorylated product, glucose 1-phosphate, cannot be transported out of the cell. Glucose 1-phosphate can then be converted to glucose 6-phosphate to enter glycolysis, meeting the energy needs of the muscle.
. Increased levels of epinephrine in the blood will:
activate adenylate cyclase in liver and muscle cells.
Carboxylation of pyruvate in humans requires ______ as an essential dietary nutrient.
biotin
compounds that can be converted to oxaloacetate can be subsequently converted to glucose. the conversion of pyruvate to glucose by gluconeogenesis requires enzymes that bypass the 3 __________ steps of glycolysis: pyruvate carboxylase and PEPCK (PEP carboxykinase) bypass pyruvate kinase fructose-1,6-bisphosphatase (FBPase) bypasses phosphofructokinase.
compounds that can be converted to oxaloacetate can be subsequently converted to glucose. the conversion of pyruvate to glucose by gluconeogenesis requires enzymes that bypass the 3 exergonic steps of glycolysis: pyruvate carboxylase and PEPCK (PEP carboxykinase) bypass pyruvate kinase fructose-1,6-bisphosphatase (FBPase) bypasses phosphofructokinase.
covalent modification of glycogen metabolism: -all occurs at the ________ -PKA = R2C2 = cyclic amp dependent PK -kinase adds phosphate --enzyme itself has 2 states; phosph and dephosph (more active phosph)
covalent modification of glycogen metabolism: -all occurs at the liver -PKA = R2C2 = cyclic amp dependent PK -kinase adds phosphate --enzyme itself has 2 states; phosph and dephosph (more active phosph)
every glycogen granule has at its core a ________ protein.
every glycogen granule has at its core a glycogenin protein.
fate of G1P: -most all converted to ________ (liver) G6P converted to glucose by G6P phosphatase and moved to blood by ________ transporter
fate of G1P: -most all converted to G6P (liver) G6P converted to glucose by G6P phosphatase and moved to blood by GLUT2
formation of glycosidic bonds requires ________ sugars
formation of glycosidic bonds requires nucleotide sugars
gluconeogenesis is regulated by changes in enzyme synthesis and by allosteric effectors, including ________, which inhibits FBPase and activates PFK (aka glycolysis) ________ synthesis depends on the phosphorylation state of the bifunctional enzyme PFK-2/FBPase-2
gluconeogenesis is regulated by changes in enzyme synthesis and by allosteric effectors, including fructose-2,6-bisphosphate (F2,6P), which inhibits FBPase and activates PFK F2,6P synthesis depends on the phosphorylation state of the bifunctional enzyme PFK-2/FBPase-2
glucose inhibits phosphorylase-a by binding to the enzymes inactive ___ state, shifting equilibrium toward the inactive __ state
glucose inhibits phosphorylase-a by binding to the enzymes inactive T state, shifting equilibrium toward the inactive T state
Both glycogen synthesis and glycogen breakdown share the metabolite ______.
glucose-1-phosphate
. An enzyme present in the endoplasmic reticulum of liver cells is ______.
glucose-6-phosphatase
Muscle cells are not able to supply glucose for other tissues because they do not contain which enzyme?
glucose-6-phosphatase
glycogen breakdown ______ is the initial monosaccharide, NOT G6P
glycogen breakdown G1P is the initial monosaccharide, NOT G6P
glycogen breakdown requires 3 enzymes. glycogen phosphorylase converts the glucosyl units at the nonreducing ends of glycogen to ____________________. Debranching enzyme transfers an alpha(1->4)-linked trisaccharide to a __________ end and hydrolyzes the alpha(1->6) linkage. __________ converts G1P to G6P. In liver, G6P is hydrolyzed by glucose-6-phosphatase to glucose for export to the tissues.
glycogen breakdown requires 3 enzymes. glycogen phosphorylase converts the glucosyl units at the nonreducing ends of glycogen to glucose-1-phosphate (G1P). Debranching enzyme transfers an alpha(1->4)-linked trisaccharide to a nonreducing end and hydrolyzes the alpha(1->6) linkage. phosphoglucomutase converts G1P to G6P. In liver, G6P is hydrolyzed by glucose-6-phosphatase to glucose for export to the tissues.
glycogen breakdowns 3 enzymes: (1)glycogen phosphorylase =>________ (2)glycogen debranching enzyme -removes branches, making more glucose residues accessible -contains 2 sepearate, different _______ ______ on one protein (3)phosphoglucomutase (G1P<=>G6P)
glycogen breakdown's 3 enzymes: (1)glycogen phosphorylase =>G-1-P (2)glycogen debranching enzyme -removes branches, making + glucose residues accessible -contains 2 sepearate, different active sites on one protein (3)phosphoglucomutase (G1P<=>G6P)
glycogen breakdown: -glycogen's highly branched structure permits rapid glucose mobilization through the simultaneous ______ of the glucose units at the end of every branch => rapid release of ________ ==(converts)==> G-6-P **mobilized by removal of non-reducing ends of glycogen (glycogen has 1 reducing end, & every branch has a ________________ end)
glycogen breakdown: -glycogen's highly branched structure permits rapid glucose mobilization through the simultaneous lysis of the glucose units at the end of every branch => rapid release of G-1-P ==(converts)==> G-6-P **mobilized by removal of non-reducing ends of glycogen (glycogen has 1 reducing end, & every branch has a non-reducing end)
glycogen debranching enzyme: -2 activities, (1) & (2) (1) shifts a __________ unit to nonreducing end (2) cleaves a(1->6) branch on remaining glucose **see slide 7
glycogen debranching enzyme: -2 activities, (1) & (2) (1) shifts a maltotriase unit to nonreducing end (2) cleaves a(1->6) branch on remaining glucose **see slide 7
glycogen is extended from a primer built on and by the protein ________
glycogen is extended from a primer built on and by the protein glycogenin
glycogen phosphorylase: **recall the 4 square model -2 states: T & R(active) -both states contains cofactor ______, derived from VitB6 -__ state has conformationally buried active site with low substrate affinity -T->R shift occurs w/presence of Ser 14-phosphoryl group
glycogen phosphorylase: **recall the 4 square model -2 states: T & R -both states contains cofactor PLP, derived from VitB6 -T state has conformationally buried active site with low substrate affinity -T->R shift occurs w/presence of Ser 14-phosphoryl group
glycogen synthesis -uses _____ as energy source=> UDP-glucose intermediate *exergonic hydrolysis of PPi from UTP
glycogen synthesis -uses UTP as energy source=> UDP-glucose intermediate *exergonic hydrolysis of PPi from UTP
glycogen synthesis requires a different pathway in which G1P is activated by reaction with UTP to form __________. Glycogen synthase adds __________ units to the nonreducing ends of a growing glycogen molecule that has been primed by glycogenic. __________ enzyme removes an alpha(1->4) linked 7-residue segment and reataches it through an alpha(1->6) linkage to form a branched chain.
glycogen synthesis requires a different pathway in which G1P is activated by reaction with UTP to form UDP-glucose. Glycogen synthase adds glucosyl units to the nonreducing ends of a growing glycogen molecule that has been primed by glycogenic. Branching enzyme removes an alpha(1->4) linked 7-residue segment and reataches it through an alpha(1->6) linkage to form a branched chain.
glycogen synthesis: -direct conversion of G1P -> glycogen & Pi is thermodynamically ________ -needs exergonic step = combining G1P with UTP=>UDPG -UDPG is able to donate ________ unit to the growing glycogen chain
glycogen synthesis: -direct conversion of G1P -> glycogen & Pi is thermodynamically unfavorable -needs exergonic step = combining G1P with UTP=>UDPG -UDPG is able to donate glycosyl unit to the growing glycogen chain
glycogen synthesis: (1) initiation of glycogen polymer synthesis ??revisit slide #8
glycogen synthesis: (1) initiation of glycogen polymer synthesis ??revisit slide #8
glycogen: -a branched polymer -polymer of a (________) linked D-glucose with a(________)-linked branches
glycogen: -a branched polymer -polymer of a(1->4) linked D-glucose with a(1->6)-linked branches
hormones such as glucagon, epinephrine, and insulin control glycogen metabolism. hormone signals that generate _____ as a second messenger or that elevate intracellular _____, which binds to the calmodulin subunit of phosphorylase kinase, promote glycogen breakdown. __________ stimulates glycogen synthesis in part by activating phosphoprotein phosphatase-1
hormones such as glucagon, epinephrine, and insulin control glycogen metabolism. hormone signals that generate cAMP as a second messenger or that elevate intracellular Ca2+, which binds to the calmodulin subunit of phosphorylase kinase, promote glycogen breakdown. insulin stimulates glycogen synthesis in part by activating phosphoprotein phosphatase-1
biotin prosthetic group of pyruvate carboxylase is covalently attached to a ______ residue of the enzyme?
lysine
mem. slide 16
mem. slide 16
The ______produces the hormones insulin and glucagon
pancreas
Which enzyme catalyzes the conversion of glucose-1-phosphate to glucose-6-phosphate?
phosphoglucomutase
The first step in the breakdown of glycogen is catalyzed by ______.
phosphorylase a
enzyme that converts phosphorylase b is to the more active phosphorylase a
phosphorylase kinase
regulation of glycogen metabolism involves ________ control as well as ________ control by covalent modification of the pathway's regulatory enzymes
regulation of glycogen metabolism involves allosteric control as well as hormonal control by covalent modification of the pathway's regulatory enzymes
study slide 12
study slide 12
the ratio of phosphorylase a (_____ active) to phosphorylase b (_____ active) depends on the activity of phosphorylase kinase, which is regulated by the activity of protein kinase A (PKA), a cAMP-dependent enzymes, and on the activity of phosphotrotein phosphatase-1 (PP1). Glycogen phosphorylase is __________ by phosphorylation, whereas glycogen synthase is activated by dephosphorylation.
the ratio of phosphorylase a (more active) to phosphorylase b (less active) depends on the activity of phosphorylase kinase, which is regulated by the activity of protein kinase A (PKA), a cAMP-dependent enzymes, and on the activity of phosphotrotein phosphatase-1 (PP1). Glycogen phosphoryylase is activated by phosphorylation, whereas glycogen synthase is activated by dephosphorylation.
under ________ conditions, most of the body's glucose needs are met by gluconeogenesis from ________________ precursors (AA)
under fasting conditions, most of the body's glucose needs are met by gluconeogenesis from noncarbohydrate precursors (AA)
